# Genetics of fungal persistence and pathogenicity in mammalian hosts

> **NIH NIH R56** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $623,986

## Abstract

Project Summary
Opportunistic fungal infections can be life-threatening and difficult to treat. Identifying the
genetic and molecular mechanisms that enable fungi to persist in humans could have major
health benefits for society, potentially even enabling the development of more effective
antifungal therapies. The model organism Saccharomyces cerevisiae is itself an opportunistic
human pathogen, with many strains isolated from clinical infections. The ability to infect and
persist within humans is not universal among S. cerevisiae strains. Clinical S. cerevisiae
isolates tend to be highly heterozygous diploids that can grow at higher temperatures and
invade into surfaces. However, rigorous genetic dissection of S. cerevisiae’s persistence and
pathogenicity within mammalian hosts is needed. To begin such work, we used chromosomally-
encoded barcodes and lineage tracking to phenotype a panel of genotyped haploid progeny
from a budding yeast cross in mice. The specific cross employed was between a haploid
derivative of a clinical isolate and the reference strain. Linkage mapping identified dozens of loci
influencing fungal persistence within a mammalian host, many of which lack previously identified
candidate genes and show host organ-dependent effects. Following our work, major questions
remain unanswered, including the genetic, molecular, and physiological mechanisms underlying
yeast persistence and yeast-host interactions; how alleles at causal loci shape the phenotypes
of highly heterozygous diploids resembling clinical isolates; the role of surface attachment and
invasion in persistence and pathogenicity; and whether the effects of causal loci contributing to
fungal pathogenicity have effects that depend on host genotype. Here, we will extend our work
by (1) studying mechanisms causing yeast persistence in particular organs by cloning causal
genes in yeast, as well as by using cutting-edge microscopy and RNA-seq to analyze yeast-host
interactions; (2) testing how combinations of pathogenicity alleles combine in highly
heterozygous diploid yeast strains; (3) analyzing how the ability to attach to and invade into
surfaces influences the pathogenicity of cross progeny; and (4) examining the genetics of fungal
pathogenicity across genetically distinct mouse hosts. Our proposal will utilize the untapped
potential of the budding yeast model system to provide concrete insights into the genetics and
molecular mechanisms underlying opportunistic fungal pathogenicity.

## Key facts

- **NIH application ID:** 10874018
- **Project number:** 1R56AI171091-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Ian Michael Ehrenreich
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $623,986
- **Award type:** 1
- **Project period:** 2023-08-17 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874018

## Citation

> US National Institutes of Health, RePORTER application 10874018, Genetics of fungal persistence and pathogenicity in mammalian hosts (1R56AI171091-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10874018. Licensed CC0.

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